Eptifibatide

Approved Indications:

• Heart Failure Post-Myocardial Infarction:
  Indicated to reduce the risk of cardiovascular mortality and morbidity in patients with left ventricular systolic dysfunction (LVEF ≤40%) and clinical evidence of heart failure following an acute myocardial infarction.
• Chronic Heart Failure (NYHA Class II):
  Approved for use in patients with reduced ejection fraction (HFrEF) to reduce hospitalization and death from heart failure.
• Hypertension (Mild to Moderate):
  Approved as monotherapy or adjunct in the treatment of essential hypertension.

Off-Label Uses (Clinically Accepted):

• Primary Aldosteronism (PA):
  Used as an alternative to surgery or adjunctive therapy in patients with bilateral adrenal hyperplasia or those unable to undergo adrenalectomy.
• Polycystic Ovary Syndrome (PCOS):
  Occasionally used for treating hyperandrogenic symptoms due to its anti-androgenic properties.
• Proteinuric Chronic Kidney Disease (CKD):
  Investigated and sometimes used off-label for reducing proteinuria in diabetic or non-diabetic nephropathy, especially when used with RAAS blockers.

Route: Oral
Administration: Once daily or divided doses with or without food

Adults:

• Heart Failure Post-MI with LV Dysfunction:
• Initial: 25 mg once daily
• Titrate to 50 mg once daily within 4 weeks based on potassium levels
• Chronic Heart Failure (HFrEF, NYHA Class II):
• Initial: 25 mg once daily
• Target: 50 mg once daily after 4 weeks if serum potassium remains <5.0 mEq/L
• Hypertension:
• Start: 50 mg once daily
• Maximum: 50 mg twice daily if necessary

Special Populations:

• Renal Impairment:
• eGFR 30–49 mL/min/1.73m²: Start at 25 mg every other day; monitor potassium frequently
• eGFR <30 mL/min/1.73m²: Not recommended
• Hepatic Impairment:
• Mild to moderate: No dose adjustment needed
• Severe impairment: Use with caution; limited data available
• Elderly:
• Start at lower end of dose range and monitor electrolytes and renal function more frequently
• Pediatric Use:
• Safety and efficacy not established

Eplerenone is a selective aldosterone receptor antagonist that binds competitively to mineralocorticoid receptors in the distal renal tubules. By inhibiting aldosterone, it blocks sodium reabsorption and promotes sodium and water excretion while conserving potassium. Unlike spironolactone, it has minimal affinity for androgen and progesterone receptors, resulting in fewer endocrine-related side effects. The net result is reduced preload and afterload, improved cardiac remodeling, and decreased myocardial fibrosis, which benefit patients with heart failure and reduce blood pressure in hypertensive individuals.

• Absorption:
  Rapidly absorbed; peak plasma concentration in ~1.5 hours post-dose
• Bioavailability:
  ~69%
• Distribution:
  Volume of distribution: ~50 L; ~50% bound to plasma proteins
• Metabolism:
  Extensively metabolized by hepatic CYP3A4 to inactive metabolites
• Half-Life:
  Terminal elimination half-life ~4 to 6 hours
• Excretion:
  Primarily excreted in urine (67%) and feces (32%) as metabolites

• Pregnancy:
  Former FDA Category B.
  Animal studies show no fetal harm, but adequate human data are lacking. Use only if clearly needed.
• Lactation:
  It is unknown whether Eplerenone is excreted into human breast milk. Animal studies suggest excretion in milk. Use caution; consider discontinuing breastfeeding or the drug depending on clinical necessity.

• Primary Class:
  Aldosterone Antagonist
• Subclass:
  Selective Mineralocorticoid Receptor Antagonist (MRA)
• Generation:
  Second-generation (more selective than spironolactone)

• Hypersensitivity to Eplerenone or any component of the formulation
• Serum potassium >5.5 mEq/L at initiation
• Creatinine clearance <30 mL/min
• Concomitant use with potassium supplements or potassium-sparing diuretics
• Use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir)
• Type 2 diabetes with microalbuminuria (when used for hypertension)

• Hyperkalemia Risk:
  Monitor serum potassium before starting, within 1 week, and periodically thereafter. Dose adjustments or discontinuation may be required.
• Renal Impairment:
  Increased risk of hyperkalemia; frequent monitoring essential.
• Hepatic Impairment:
  Use with caution; limited clinical data in severe impairment.
• Drug Interactions:
  Avoid use with CYP3A4 inhibitors and drugs that raise potassium levels.
• Monitoring Required:
• Serum potassium
• Renal function (eGFR, serum creatinine)
• Blood pressure
• Signs of Severe Reactions:
• Cardiac arrhythmias (from hyperkalemia)
• Unexplained muscle weakness, fatigue (suggestive of electrolyte imbalance)

Common (≥1%):

• Electrolyte & Renal:
• Hyperkalemia
• Increased creatinine
• Hypotension
• Gastrointestinal:
• Diarrhea
• Nausea
• General:
• Fatigue
• Dizziness

Less Common / Serious:

• Cardiovascular:
• Bradycardia
• Ventricular arrhythmias (from elevated potassium)
• Endocrine/Metabolic:
• Hyponatremia
• Dehydration
• Rare Allergic Reactions:
• Rash
• Pruritus
• Angioedema (rare)

• Major CYP3A4 Inhibitors (Contraindicated):
• Ketoconazole, Itraconazole, Clarithromycin, Telithromycin, Ritonavir, Nefazodone
• Potassium-Retaining Drugs (Additive Risk of Hyperkalemia):
• Potassium supplements, Spironolactone, Amiloride, Triamterene, ACE inhibitors, ARBs, NSAIDs
• CYP3A4 Inducers (May Reduce Effectiveness):
• Rifampin, St. John’s Wort, Carbamazepine, Phenytoin
• Lithium:
  Increased risk of lithium toxicity
• NSAIDs:
  May impair renal function and potentiate hyperkalemia

• 2022 ACC/AHA/HFSA Heart Failure Guidelines:
  Eplerenone continues to be recommended as part of guideline-directed medical therapy for HFrEF to reduce hospitalization and mortality.
• Labeling Update (Recent Years):
  Emphasis on tighter monitoring protocols for potassium in high-risk populations and expanded use in early-stage heart failure (NYHA Class II).
• EMA Updates:
  Reinforced warnings on avoiding use with potassium-sparing diuretics and mandatory electrolyte monitoring.

• Store below 25°C (77°F)
• Protect from moisture and light
• Keep in the original container
• Do not refrigerate or freeze
• No shaking or reconstitution required